Abstract
The pathophysiology of refractory chronic cough (RCC) is unclear. We hypothesised that endogenous inhibitory control mechanisms, such as those activated by noxious stimuli inducing pain (conditioned pain modulation) may be capable of inhibiting coughing and urge to cough evoked by inhaled capsaicin. Furthermore, these mechanisms may be impaired in patients with RCC.
The objective was to investigate the effects of pain on cough and urge to cough in healthy volunteers and RCC patients. Healthy volunteers and RCC patients underwent a randomised, controlled, four-way crossover study comparing the effect of four interventions on capsaicin-evoked coughing and urge to cough. The interventions comprised immersing a hand in 1) noxious cold water; 2) warm water; 3) warm water, but subjects were instructed to voluntarily supress coughing; and 4) no intervention. The co-primary outcomes were numbers of evoked coughs and urge to cough scores.
20 healthy volunteers (mean±sd age 50.1±14.2 years, male:female 10:10) and 20 RCC patients (age 60.1±7.9 years, male:female 9:11) participated. Overall, noxious cold water reduced capsaicin-evoked urge-to-cough scores and cough numbers compared with warm water (1.6 (95% CI 1.3–2.0) versus 2.2 (1.8–2.6), p<0.001 and 4.8 (3.7–6.2) coughs versus 7.9 (6.7–9.5) coughs, p<0.001, respectively). Healthy volunteers and RCC patients demonstrated similar reductions in the urge to cough during noxious cold-water immersion, but noxious cold water and voluntary suppression interventions were less effective at reducing capsaicin-evoked cough in RCC patients than in healthy volunteers (p=0.041).
Endogenous inhibitory control mechanisms, specifically those activated by pain, can reduce both coughing and the urge to cough. Impairment of endogenous inhibitory control mechanisms may contribute to excessive coughing in RCC.
Abstract
Painful cold-water hand immersion elicited a weaker inhibitory effect on cough in patients with refractory chronic cough than healthy volunteers, suggesting a relative deficiency in conditioned pain modulation https://bit.ly/3gedtjg
Footnotes
This article has supplementary material available from erj.ersjournals.com
This study is registered at www.isrctn.com with clinical trial identifier ISRCTN31901405.
Author contributions: Conception and design: E. Hilton and J.A. Smith; participant screening and recruitment; E. Hilton and K. Holt; data analysis and interpretation: E. Hilton, I. Satia, J. Belcher and J.A. Smith; drafting the manuscript: I. Satia, J.A. Smith. All authors approved the final manuscript submission.
Conflict of interest: E. Hilton has nothing to disclose.
Conflict of interest: I. Satia reports personal fees for lectures from GSK and AstraZeneca, grants and personal fees from Merck Canada, grants from ERS Respire 3 Marie Curie Fellowship, outside the submitted work.
Conflict of interest: K. Holt has nothing to disclose.
Conflict of interest: A.A. Woodcock reports personal fees from GlaxoSmithKline, Novartis, Chiesi, Axalbion, Reacta Biotech, and from the Medicines Evaluation Unit, outside the submitted work; and is a named inventor on a patent, owned by Manchester University NHS Foundation Trust and licensed to Vitalograph Ltd, describing the detection of cough from sound recordings.
Conflict of interest: J. Belcher has nothing to disclose.
Conflict of interest: J.A. Smith reports grants and personal fees for consultancy and lectures from GlaxoSmithKline, grants and personal fees for consultancy from NeRRe Pharmaceuticals, Menlo, Axalbion, Afferent, Merck and Bayer, personal fees for consultancy from Boehringer Ingelheim, Genentech, Neomed, Chiesi, Bellus, AstraZeneca and Algernon, non-financial support (provision of equipment) from Vitalograph, outside the submitted work; and is a named inventor on a patent, owned by Manchester University NHS Foundation Trust and licensed to Vitalograph Ltd, describing the detection of cough from sound recordings.
Support statement: E. Hilton and this study were funded by a Medical Research Council doctoral fellowship (ID: 91870). I. Satia was supported by the European Respiratory Society Respire 3 Fellowship (R3201703-00122). The study was conducted with the support of the National Institute of Health Research (NIHR) Manchester Clinical Research Facility. J.A. Smith is funded by the NIHR Manchester Biomedical Research Centre, a Wellcome Investigator in Science Award and is an NIHR Senior Investigator. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received April 27, 2020.
- Accepted June 28, 2020.
- Copyright ©ERS 2020